Kaposi's sarcoma complicating corticosteroid therapy for temporal arteritis.

Combination immunosuppressive therapy, particularly in renal transplant recipients, is associated with a higher than expected risk of development of Kaposi's sarcoma, In this report, cutaneous dissemination of Kaposi's sarcoma occurred in a patient with temporal arteritis who was treated with corticosteroids. Reduction of the steroid dosage was followed by regression of the tumor. This sequence of events suggests a causal relationship between the evolution of the sarcoma and corticosteroid therapy. Although Kaposi's sarcoma may complicate corticosteroid therapy alone, the incidence is considerably lower than in renal transplant recipients receiving combination immunosuppressive therapy. Considering the large number of patients with temporal arteritis who are treated with steroids and that this is the first report of its association with Kaposi's sarcoma, it seems that other factors, perhaps genetic, might be important in the development of this neoplasm.

Desensitization to allopurinol in patients with gout and cutaneous reactions.

PURPOSE: To determine the efficacy and safety of slow oral desensitization in the management of allopurinol-related pruritic cutaneous eruptions. PATIENTS AND METHODS: Nine patients with renal insufficiency and chronic tophaceous gouty arthritis, who had to interrupt their allopurinol therapy because of an allergic-type pruritic maculopapular eruption, were enrolled in an allopurinol oral desensitization protocol using a schedule of gradually increasing doses. RESULTS: Cautious reinstitution of allopurinol was successfully accomplished in all nine patients, but four individuals required dose adjustment because of development of a mild, recurrent, macular rash early during the protocol at allopurinol doses of less than or equal to 5 mg/d. Transient, postdesensitization cutaneous reactions occurred in two patients, one of whom also had an early rash. CONCLUSION: Oral desensitization to the minor rashes induced by allopurinol is a feasible and acceptably safe approach to therapy, particularly for those with renal insufficiency in whom no substitute urate-lowering drug is available.

Recent advances in the management of adult myositis.

Standard drug therapy of adult polymyositis, dermatomyositis and inclusion body myositis includes high-dose corticosteroids and cytotoxic drugs (methotrexate, azathioprine (AZA) and cyclophosphamide). Recent data are in favour of the early introduction of a cytotoxic or immunomodulating drug in addition to corticosteroid therapy. In patients with corticosteroid- and cytotoxic-resistant myositis, promising novel approaches to management include: iv. megadose pulse methylprednisolone combined with cytotoxic drugs, combination therapy with both methotrexate and AZA, cyclosporin, tacrolimus, fludarabine and iv. immunoglobulin (IVIG). Recent advances in the understanding of the role of cytokines and complement, in the pathogenesis of myositis, have led to preliminary therapeutic trials of three biological agents: etanercept, infliximab and anti-C5 monoclonal antibody.

Gout in the elderly. Clinical presentation and treatment.

Gout in the elderly differs from classical gout found in middle-aged men in several respects: it has a more equal gender distribution, frequent polyarticular presentation with involvement of the joints of the upper extremities, fewer acute gouty episodes, a more indolent chronic clinical course, and an increased incidence of tophi. Long term diuretic use in patients with hypertension or congestive cardiac failure, renal insufficiency, prophylactic low dose aspirin (acetylsalicylic acid), and alcohol (ethanol) abuse (particularly by men) are factors associated with the development of hyperuricaemia and gout in the elderly. Extreme caution is necessary when prescribing nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of acute gouty arthritis in the elderly. NSAIDs with short plasma half-life (such as diclofenac and ketoprofen) are preferred, but these drugs are not recommended in patients with peptic ulcer disease, renal failure, uncontrolled hypertension or cardiac failure. Colchicine is poorly tolerated in the elderly and is best avoided. Intra-articular and systemic corticosteroids are increasingly being used for treating acute gouty flares in aged patients with medical disorders contraindicating NSAID therapy. Urate-lowering drugs are indicated for the treatment of hyperuricaemia and chronic gouty arthritis. Uricosuric drugs are poorly tolerated and the frequent presence of renal impairment in the elderly renders these drugs ineffective. Allopurinol is the urate-lowering drug of choice, but its use in the aged is associated with an increased incidence of both cutaneous and severe hypersensitivity reactions. To minimise this risk, allopurinol dose must be kept low. A starting dose of allopurinal 50 to 100mg on alternate days, to a maximum daily dose of about 100 to 300mg, based upon the patient's creatinine clearance and serum urate level, is recommended. Asymptomatic hyperuricaemia is not an indication for long term urate-lowering therapy; the risks of drug toxicity often outweigh any benefit.

Approach to musculoskeletal chest wall pain.

Pain in the chest may be the presenting feature of a diverse number of musculoskeletal chest wall conditions. The more common causes are costochondritis, trauma to the chest wall, benign overuse myalgia, fibrositis, referred pain, and psychogenic regional pain syndrome. These disorders are often mistaken for angina pectoris and other serious disorders. Information about onset, location, character, duration and modulating factors of the pain and other symptoms, a meticulous examination of the ribs, spine, sternum and their articulations, and a few judiciously selected diagnostic studies will establish the diagnosis in most patients. Knowledge and understanding of the underlying pathogenic mechanisms of these musculoskeletal disorders is important for optimal management.

Managing problem gout.

For the management of acute gouty arthritis, non-steroidal anti-inflammatory drugs (NSAIDs) are the drugs of choice. In recent years, the use of colchicine has declined because of its frequent adverse reactions, and its reduced efficacy when administered more than 24 hours after onset of an acute attack. Intra-articular corticosteroid therapy (e.g. methylprednisolone acetate) is indicated for the treatment of acute mono or oligoarticular gouty arthritis in aged patients, and in those with co-morbid conditions contraindicating therapy with either NSAIDs or colchicine. Oral corticosteroids (e.g. prednisone), and both parenteral corticotrophin (ACTH) and corticosteroids (e.g. intramuscular triamcinolone acetonide) are valuable, relatively safe alternate treatment modalities in those with polyarticular attacks. For the treatment of hyperuricaemia and chronic gouty arthritis, allopurinol is the preferred urate-lowering drug. Its toxicity in elderly individuals, those with renal impairment, and in cyclosporine-treated transplant patients can be minimised by adjusting the initial dose according to the patient's creatinine clearance. In those experiencing cutaneous reactions to allopurinol, cautious desensitisation to the drug can be achieved using a schedule of gradually increasing doses. The therapeutic usefulness of uricosuric drugs is limited by the presence of renal impairment, occurrence of intolerable side-effects, or concomitant intake of salicylates. They are particularly indicated in patients allergic to allopurinol and in those with massive tophi requiring combined therapy with both allopurinol and a uricosuric.

Acute calcium pyrophosphate dihydrate crystal-induced tenosynovitis.

Calcium pyrophosphate dihydrate crystal deposition in tendon sheaths is a rare cause of acute and chronic tenosynovitis. An elderly patient with acute wrist pyrophosphate tenosynovitis and transient periarticular calcification is described.

What is new about crystals other than monosodium urate?

Recently, attention has focused on the effects of weather conditions and seasonal changes on the incidence of acute microcrystalline events. Acute gout attacks are more frequent during the spring, but seasonal variations in the incidence of acute pseudogout attacks are less clearly defined. Genetic analysis of two unrelated families with calcium pyrophosphate dihydrate (CPPD) crystal deposition disease showed linkage to the short arm of chromosome 5p. Several recent reports show CPPD crystal disease occurring in association with Gitelman syndrome, the hypocalciuric-hypomagnesemic variant of Bartter syndrome. Two signaling pathways, protein kinase C and adenyl cyclase, modulate generation of extracellular pyrophosphate by porcine cartilage chrondrocytes. These transduction mechanisms may provide potential targets for the treatment of CPPD crystal deposition disease. A controlled clinical trial showed ultrasound therapy to be beneficial in the treatment of symptomatic chronic calcific tendinitis of the shoulder. There is evidence that apatite crystals may contribute to cartilage damage in osteoarthritis and that therapeutic interventions to prevent the formation and biologic effects of the crystals may potentially retard the progression of the osteoarthritic process.

Calcium pyrophosphate crystal deposition disease and other crystal deposition diseases.

"Tumoral" calcium pyrophosphate dihydrate (CPPD) crystal deposition in the ligamentum flavum is rare and can lead to compression myeloradiculopathy in the cervical spine and to spinal canal stenosis in the lumbar spine. CPPD crystal deposition disease is rarely associated with Bartter's syndrome and hypomagnesemia. Intramuscular corticotropin has proved effective in the treatment of acute episodes of pyrophosphate arthritis in patients with multiple medical illnesses in whom nonsteroidal anti-inflammatory drugs are contraindicated. IgG binding to CPPD crystals enhances neutrophil activation (by increasing intracellular cytoplasmic calcium levels) and seems to play a greater role in pyrophosphate than in urate crystal-induced inflammation. Transforming growth factor-beta 1 stimulates intracellular pyrophosphate generation by articular chondrocytes. The effect is inhibited by probenecid, an anion transport blocker, through interfering with the active transport of intracellular pyrophosphate to cartilage matrix where crystals form. Calcific tendinitis associated with underlying cortical bone erosions is an uncommon manifestation of apatite crystal deposition disease. Closed-needle tidal irrigation proved beneficial in two patients with Milwaukee shoulder syndrome. Two patients with nodular subcutaneous cholesterol crystal deposition are described.

Difficult gout and new approaches for control of hyperuricemia in the allopurinol-allergic patient.

A major obstacle to the treatment of hyperuricemia in patients allergic to allopurinol is the limited availability of suitable, equally effective, alternative, urate-lowering drugs. Conventional uricosuric drugs, including probenecid and sulfinpyrazone, are recommended for allopurinol- intolerant patients with gout and "underexcretion" hyperuricemia who have normal renal function and no history of nephrolithiasis. Therapeutic options in those in whom traditional uricosuric drugs are contraindicated, ineffective, or poorly tolerated include slow oral desensitization to allopurinol and cautious administration of oxipurinol. Allopurinol desensitization is useful particularly in those who have failed other treatment modalities. If available (as in Europe, South Africa, and Japan), benzbromarone may be tried in patients with gout and mild-to-moderate renal insufficiency. Recombinant urate oxidase can be used in the short-term prophylaxis and treatment of chemotherapy- associated hyperuricemia in patients with lymphoproliferative and myeloproliferative disorders. Hyperuricemia and gout occur with increased frequency in cyclosporine-treated allograft transplant recipients. The management of gout in these patients is complicated by two main factors: cyclosporine-induced renal impairment, and interactions with medications used to preserve the allograft.

Current therapy of acute microcrystalline arthritis and the role of corticosteroids.

The management of acute gout, and other acute microcrystalline arthritides, can be difficult in aged patients, and in those with multiple medical illnesses contraindicating therapy with either nonsteroidal anti-inflammatory drugs or colchicine. Intra-articular corticosteroid therapy is particularly useful for the treatment of acute mono-or oligo-articular micro-crystalline synovitis in these patients. Oral corticosteroids (e.g., prednisone), and both parenteral corticotrophin (adrenocorticotrophic hormone) (ACTH) and corticosteroids (e.g., triamcinolone acetonide, methylprednisolone acetate), are useful alternate treatment modalities in those patients with acute polyarticular attacks. Although ACTH has demonstrated comparable clinical efficacy to corticosteroids in the treatment of acute micro-crystalline events, corticosteroids are preferred by many physicians for many reasons: administration can be oral, dose can be regulated precisely, effectiveness does not depend on adrenocortical responsiveness, and incidence of certain side effects, such as hypertension and fluid overload, is lower.

Calcium pyrophosphate crystal deposition disease and other crystal deposition diseases.

A number of cells, chemotactic factors, and inflammatory mediators are implicated in the complex mechanisms underlying crystal-mediated inflammation. Interleukin-8, released from mononuclear cells that have been exposed to urate and other crystals, is a potent chemotaxin and activator of neutrophils. Experimental and clinical observations suggest that joint movements, local biomechanical factors, and previous joint damage may play a role in influencing the intensity of microcrystalline synovitis and the distribution of articular and periarticular crystal deposits in both calcium pyrophosphate dihydrate crystal deposition disease and gout. There are rare reports of extra-articular calcium pyrophosphate dihydrate crystal deposition in tendons, bursae, dura mater, and ligamentum flavum (with radiculomyelopathy) and of massive "tumoral," tophuslike, periarticular calcium pyrophosphate dihydrate crystal deposits. Synovial fluid levels of ATP, the main substrate for nucleoside triphosphate pyrophosphohydrolase ectoenzyme, which cleaves ATP-releasing inorganic pyrophosphate, are higher in patients with calcium pyrophosphate dihydrate crystal deposition disease than in those with other arthritides, and the levels correlate with inorganic pyrophosphate concentrations. Further reports of acute calcific periarthritis of the first metatarsophalangeal joint (hydroxyapatite pseudopodagra) in young women have been described. The mitogenic response of fibroblasts to stimulation with basic calcium phosphate crystals is accompanied by induction and secretion of collagenase and neutral proteases, implicating a role for the crystals in the pathogenesis of both synovial proliferation and joint damage in chronic basic calcium phosphate crystal-associated arthropathy. Subcutaneous cholesterol crystal deposition with tophus formation is extremely rare and has been described in a patient with scleroderma and calcinosis cutis.

Paraneoplastic rheumatic syndromes.

Malignant neoplasms are associated with a wide variety of paraneoplastic rheumatological syndromes. Among these, hypertrophic osteoarthropathy, carcinoma polyarthritis, dermatomyositis/polymyositis, and paraneoplastic vasculitis are the most frequently recognized. Other less known associations are based upon a smaller number of reported patients, and include fasciitis, panniculitis, erythema nodosum, Raynaud's syndrome, digital gangrene, erythromelalgia and lupus-like syndromes. Musculoskeletal manifestations of malignancy may coincide, follow or antedate the diagnosis of cancer, or herald its recurrence. The clinical course generally parallels that of the primary tumour, and treatment of the underlying malignancy often results in regression of the rheumatic disorder. Awareness that cancer can cause certain non-metastatic symptoms is important for early diagnosis and treatment of an occult neoplasm. Rheumatic manifestations suggesting a hidden cancer include: rapid onset of an unusual inflammatory arthritis clubbing or diffuse bone pains in a patient 50 years of age or older, chronic unexplained vasculitis, refractory fasciitis, Raynaud's syndrome unresponsive to vasodilator therapy, rapidly progressive digital gangrene or Lambert-Eaton myasthenic syndrome. Management consists of control of the underlying cancer and symptomatic treatment of the rheumatic syndrome with non-steroidal anti-inflammatory drugs or corticosteroids.

Another look at spinal tuberculosis.

The steady decline in tuberculosis rates in Canada has led to a certain lack of awareness of the disease. We describe 7 patients with culture proven spinal tuberculosis, seen in a teaching hospital over a 10-year period. Persistent spinal pain and local tenderness were the most frequent presenting findings. There was a mean delay in diagnosis of 5.2 (range 1-18) months from the time of presentation. Only 2 patients had active extraspinal tuberculous infection. Plain spinal radiographs were the initial diagnostic procedure of choice showing a destructive vertebral lesion in 5 of 7 patients. Computed tomography (CT) played an important role in delineating the discovertebral lesion and in demonstrating a paraspinal soft tissue infection in 6 (85%) of 7 patients: psoas abscess in 4 (2 with epidural extension), epidural abscess in one, and a neck abscess in one. Magnetic resonance imaging (MRI) in one patient enabled a more complete definition of the vertebral infection and its soft tissue extensions. Two patients were successfully treated with combination antituberculous chemotherapy alone, and 5 required adjuvant surgical procedures. Our study stresses the need for increased alertness to this now uncommon but treatable spinal infection, and emphasizes the diagnostic usefulness of CT and MRI in defining subtle discovertebral lesions and in detecting unsuspected paravertebral soft tissue extension.

Treatment of fulminant adult Still's disease with intravenous pulse methylprednisolone therapy.

We describe a patient with fulminant adult onset Still's disease and multiple organ involvement. The acute flare persisted despite high doses of prednisone but responded to megadose intravenous pulse methylprednisolone therapy. This treatment modality may be useful in temporizing severe multisystem exacerbations of adult Still's disease.

Hypertrophic osteoarthropathy, phalangeal and synovial metastases associated with bronchogenic carcinoma.

A 61-year-old woman with bronchogenic carcinoma simultaneously developed hypertrophic osteoarthropathy (HOA), phalangeal metastases, and metastatic carcinoma of the synovium. The right knee synovium showed several blood vessels containing carcinomatous cells. Although the association of HOA phalangeal and synovial metastases in this case is likely a chance occurrence, awareness of this possibility is extremely valuable as it has important therapeutic implications.

Unusual metacarpophalangeal osteoarthritis in a jackhammer operator.

Severe, atypical osteoarthritis of the metacarpophalangeal and elbow joints in a jackhammer operator is reported. Articular tissue resected at surgery demonstrated gross fibrillation and histologic evidence of calcification of articular cartilage, and multiple, bony fragments embedded in the synovium. Operation of a pneumatic drill may accentuate a tendency toward development of osteoarthritis in workers who are predisposed to the disease and may also cause it to localize at unusual sites such as the elbow, shoulder, wrist, and metacarpophalangeal joints.

Intradermal urate tophi.

OBJECTIVE: To analyze the clinical features and identify risk factors associated with the development of intradermal urate tophi. METHODS: Six patients (5 men and 1 woman, mean age 59.8 yrs) with intradermal tophi were studied between 1987 and 1996. RESULTS: Intradermal urate crystal deposits appeared as small, superficial, pustule-like, whitish lesions. All patients experienced superimposed inflammatory episodes with increasing pain, swelling, and erythema of the intradermal tophi. In one patient, the lesions were associated with a peculiar skin hyperpigmentation. Five had intermittent liquefaction and ulcerations of the lesions with drainage of white chalky matter from which monosodium urate crystals were recovered. Mean pre-treatment serum urate was 570.6 mumol/l (range 496-720). Risk factors for gout and intradermal tophi included renal failure in all 6, hypertension and chronic diuretic therapy in 4, and one patient each with alcohol abuse, chronic low dose acetylsalicylic acid, myeloma, and a positive family history. CONCLUSION: Intradermal urate tophi with superimposed inflammatory episodes, intermittent ulcerations, and possibly pigmentary changes, are rare skin manifestations of chronic tophaceous gout. Renal insufficiency, hypertension, and chronic diuretic use are factors associated with the development of hyperuricemia and gout in these patients.

Acute calcific periarthritis in scleroderma.

Three patients with limited cutaneous scleroderma (CREST syndrome) and acute calcific periarthritis are presented. "Chalky" bursal effusion in one patient demonstrated masses of calcium hydroxyapatite crystals. In contrast to idiopathic acute calcific periarthritis, resorption of periarticular calcifications after resolution of acute attacks occurs both less frequently and incompletely in scleroderma associated acute calcific periarthritis.

Musculoskeletal chest wall pain.

The musculoskeletal structures of the thoracic wall and the neck are a relatively common source of chest pain. Pain arising from these structures is often mistaken for angina pectoris, pleurisy or other serious disorders. In this article the clinical features, pathogenesis and management of the various musculoskeletal chest wall disorders are discussed. The more common causes are costochondritis, traumatic muscle pain, trauma to the chest wall, "fibrositis" syndrome, referred pain, psychogenic regional pain syndrome, and arthritis involving articulations of the sternum, ribs and thoracic spine. Careful analysis of the history, physical findings and results of investigation is essential for precise diagnosis and effective treatment.